Molecular medicine (Cambridge, Mass.) · 2017
IL-37 suppresses MyD88-mediated inflammatory responses in human aortic valve interstitial cells.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhan Qiong, Zeng Qingchun, Song Rui, Zhai Yufeng, Xu Dingli, Fullerton David A, Dinarello Charles A, Meng Xianzhong
Аннотация
BACKGROUND: Calcific aortic valve disease (CAVD) is common among the elderly, and aortic valve interstitial cells (AVICs) exhibit unique inflammatory and osteogenic responses to pro-inflammatory stimulation which play an important role in valvular fibrosis and calcification. Thus, suppression of AVIC pro-inflammatory response may have therapeutic utility for prevention of CAVD progression. Interleukin (IL)-37, an anti-inflammatory cytokine, reduces tissue inflammation.
OBJECTIVE: This study was to test the hypothesis that IL-37 suppresses human AVIC inflammatory responses to Toll-like receptor (TLR) agonists.
METHODS AND RESULTS: Human AVICs were exposed to Pam3CSK4, poly(I:C) and lipopolysaccharide, respectively, in the presence and absence of recombinant human IL-37. Stimulation of TLR4 increased the production of intercellular adhesion molecule-1, IL-6, IL-8 and monocyte chemoattractant protein-1. Knockdown of myeloid differentiation factor 88 (MyD88) or TIR-domain-containing adaptor inducing interferon-β (TRIF) differentially affected inflammatory mediator production following TLR4 stimulation. IL-37 reduced the production of these inflammatory mediators induced by TLR4. Moreover, knockdown of IL-37 enhanced the induction of these mediators by TLR4. IL-37 also suppressed inflammatory mediator production induced by the MyD88-dependent TLR2, but had no effect on the inflammatory responses to the TRIF-dependent TLR3. Furthermore, IL-37 inhibited NF-κB activation induced by TLR2 or TLR4 through a mechanism dependent of IL-18 receptor α-chain.
CONCLUSION: Activation of TLR2, TLR3 or TLR4 up-regulates the production of inflammatory mediators in human AVICs. IL-37 suppresses MyD88-mediated responses to reduce inflammatory mediator production following stimulation of TLR2 and TLR4. This anti-inflammatory cytokine may be useful for suppression of aortic valve inflammation elicited by MyD88-dependent TLR signaling.
OBJECTIVE: This study was to test the hypothesis that IL-37 suppresses human AVIC inflammatory responses to Toll-like receptor (TLR) agonists.
METHODS AND RESULTS: Human AVICs were exposed to Pam3CSK4, poly(I:C) and lipopolysaccharide, respectively, in the presence and absence of recombinant human IL-37. Stimulation of TLR4 increased the production of intercellular adhesion molecule-1, IL-6, IL-8 and monocyte chemoattractant protein-1. Knockdown of myeloid differentiation factor 88 (MyD88) or TIR-domain-containing adaptor inducing interferon-β (TRIF) differentially affected inflammatory mediator production following TLR4 stimulation. IL-37 reduced the production of these inflammatory mediators induced by TLR4. Moreover, knockdown of IL-37 enhanced the induction of these mediators by TLR4. IL-37 also suppressed inflammatory mediator production induced by the MyD88-dependent TLR2, but had no effect on the inflammatory responses to the TRIF-dependent TLR3. Furthermore, IL-37 inhibited NF-κB activation induced by TLR2 or TLR4 through a mechanism dependent of IL-18 receptor α-chain.
CONCLUSION: Activation of TLR2, TLR3 or TLR4 up-regulates the production of inflammatory mediators in human AVICs. IL-37 suppresses MyD88-mediated responses to reduce inflammatory mediator production following stimulation of TLR2 and TLR4. This anti-inflammatory cytokine may be useful for suppression of aortic valve inflammation elicited by MyD88-dependent TLR signaling.